Parkinson’s disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra (SN), accumulation of alpha-synuclein (a-Syn)-rich aggregates, and the development of both motor and non-motor symptoms. The absence of a cure for PD underscores the critical need for animal models that recapitulate both its molecular hallmarks and the spectrum of behavioral symptoms to elucidate pathogenic mechanisms and advance therapeutic development. While the virus-mediated a-Syn overexpression rat model recapitulates progressive dopaminergic neurodegeneration and motor deficits, its non-motor phenotypic profile remains poorly characterized. In this study, we investigated the behavioral consequences of targeted adeno-associated virus (AAV)-mediated overexpression of aggregate-prone mutant A53T a-Syn within the rat SN bilaterally. We confirmed dopaminergic neurodegeneration within 6 weeks, along with progressive motor impairments evident as reduced locomotion in the open field test and increased foot slips in the grid walking test as early as 3 weeks post-AAV injection. The dopaminergic origin of the motor deficit in the grid walking was confirmed at the 6-week timepoint by its attenuation with L-DOPA treatment. Crucially, animals overexpressing A53T a-Syn exhibited reduced responsiveness to palatable stimulation in the sucrose preference test in the context of advanced neurodegeneration. No changes in anxiety-like behaviors, olfactory function, or recognition memory were observed when compared with age-matched controls. These findings suggest that, in addition to motor impairments, bilateral A53T a-Syn overexpression induces depression-like behavior, providing a valuable tool for studying the pathogenesis and treatment of non-motor affective symptoms in PD.
Robot-assisted distal pancreatectomy (RDP) was developed to overcome technical limitations of laparoscopic distal pancreatectomy (LDP), yet uncertainty persists regarding oncologic adequacy, learning-curve effects, and outcomes in high-risk subgroups. We synthesized current evidence to address these gaps. We systematically searched PubMed and EMBASE, in accordance with PRISMA guidelines, from inception to 2025 to identify comparative studies of RDP versus LDP. Using random-effects models, we calculated weighted mean differences (WMDs) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes, and performed subgroup analyses, including pancreatic ductal adenocarcinoma (PDAC), along with meta-regression to explore heterogeneity sources. Sixty-four studies comprising 15,790 patients (5,723 RDP; 10,067 LDP; mean age 60.5 years; BMI 26.1 kg/m²) were included. RDP resulted in lower blood loss (WMD − 52.0 mL; p < 0.00001), fewer conversions (RR 0.49; p < 0.00001), and fewer unplanned splenectomies (RR 0.59; p < 0.0001). Operative time was longer (WMD + 24.06 min; p < 0.00001). Postoperative morbidity, POPF, PPH, infection, reintervention, and mortality were comparable. Length of stay was shorter with RDP (WMD − 0.57 days; p < 0.00001). Although lymph node yield appeared higher with LDP in the overall and PDAC cohorts, this difference was no longer significant in a sensitivity analysis, and R0 resection rates remained comparable. Costs were higher with RDP, with substantial heterogeneity. RDP and LDP demonstrate comparable safety and oncologic outcomes. RDP reduces blood loss, conversions, and splenectomy but increases operative time and cost. The operative time disadvantage likely reflects learning-curve. Selective use in high-risk and complex resections is supported; cost-effectiveness warrants further study.
Cardiovascular disease is the leading cause of mortality among individuals with kidney failure, yet evidence-based strategies to reduce cardiovascular risk in this population are limited. Kidney transplantation has been consistently shown to improve survival, including cardiovascular-specific outcomes among those with kidney failure. Substantial heterogeneity exists across transplant centers regarding the pre-transplant cardiovascular evaluation, and the evidence supporting specific testing strategies remains sparse. Current scientific guidelines and consensus statements on pre-kidney transplant cardiovascular assessment, which guide clinical practice, recommend asymptomatic testing in most individuals. However, emerging retrospective evidence suggests limited short-term benefit from routine asymptomatic screening. Ongoing randomized studies may clarify optimal strategies for repeat cardiovascular screening in waitlisted individuals who have undergone initial cardiovascular evaluation. In this review of kidney transplant candidates, we (i) examine contemporary data on cardiovascular screening (ii) highlight the diagnostic limitations of noninvasive testing in kidney failure and the lack of clear benefit from revascularization in the pre-kidney transplant setting, and (iii) outline the consequences of untimely and potentially unnecessary cardiovascular testing.
Used to suppress inflammation, preoperative corticosteroid exposure is common among patients undergoing total knee arthroplasty (TKA). New preclinical evidence links corticosteroid exposure to developing chronic pain, which may lead to long-term opioid treatment. We aimed to explore whether there is an association between preoperative corticosteroid exposure and persistent opioid requirements in previously opioid-naïve patients undergoing TKA. In an exploratory retrospective cohort study, we searched a nationwide USA claims database for patients who were opioid-naïve and underwent primary TKA between January 2010 and October 2022. Our primary objective was to explore the magnitude of any association between preoperative corticosteroid claims (oral/parenteral/intra-articular) and postoperative opioid prescription claims at 3 months using multivariable logistic regression. Our secondary objective was to explore the association at 6 months. The matched cohort included 763,530 patients who were opioid-naïve; of those, 27,510 did and 736,020 did not have preoperative corticosteroid claims within 30 days of TKA. At 3 months, 5,015 patients (18.2
To examine the combined and separate impacts of traumatic brain injury (TBI) and interpersonal violence on new and severe mental illness in the postpartum period. We undertook a population-based cohort study of 1,090,139 births in Ontario, Canada, 2012–2021. We stratified the cohort by pre-delivery history of mental health care to identify (i) new episodes of mental illness and (ii) severe mental illness within 365 days of childbirth. Modified Poisson regression was used to calculate adjusted relative risks (aRR) of these outcomes in individuals with a history of TBI and violence, TBI alone, and violence alone versus neither (referent). Then, we calculated adjusted relative excess risk due to interaction (aRERI) to quantify the super-additive risk related to the presence of both factors. The risk of any new episode of mental illness postnatally was greatest in individuals with a history of both TBI and violence (aRR 1.58; 95
